Design, synthesis, biological evaluation and in silico studies of EGFR inhibitors based on 4-oxo-chromane scaffold targeting resistance in non-small cell lung cancer (NSCLC).

Allosteric kinase inhibitors targets kinases with oncogenic driver mutations in malignancies as a potential new therapy strategy. EGFR inhibitors with a 4-oxo-chromane scaffold targeting the L858R/T790M/C797S mutation were identified, optimized, synthesized, and assessed for anticancer and EGFR enzyme inhibitory activity. Compounds 4i and 4l were shown to be very effective with IC₅₀ values of 132 and 146 nM, respectively, and excellent selectivity in in silico study. Compound 4i showed substantial antioxidant activity at a concentration of 100 µM, with a DPPH radical scavenging value of 91.46%. The synthesized compounds 4i, 4k and 4l were found to be selective toward cancer cells since they did not exhibit cytotoxicity even at IC₅₀ > 20 µM on normal cells. Compound potency was further assessed using in silico and in vitro biological evaluation. [ABSTRACT FROM AUTHOR]